The orphan receptor CRF2-4 is an essential subunit of the interleukin 10 receptor.
The orphan receptor CRF2-4 is a member of the class II cytokine receptor family (CRF2), which includes the interferon receptors, the interleukin (IL) 10 receptor, and tissue factor. CRFB4, the gene encoding CRF2-4, is located within a gene cluster on human chromosome 21 that comprises three interferon receptor subunits. To elucidate the role of CRF2-4, we disrupted the CRFB4 gene in mice by means of homologous recombination. Mice lacking CRF2-4 show no overt abnormalities, grow normally, and are fertile. CRF2-4 deficient cells are normally responsive to type I and type II interferons, but lack responsiveness to IL-10. By approximately 12 wk of age, the majority of mutant mice raised in a conventional facility developed a chronic colitis and splenomegaly. Thus, CRFB4 mutant mice recapitulate the phenotype of IL-10-deficient mice. These findings suggest that CRF2-4 is essential for IL-10-mediated effects and is a subunit of the IL-10 receptor.
Spencer
S D
SD
Genentech Inc., South San Francisco, California 94080, USA.
Di Marco
F
F
Hooley
J
J
Pitts-Meek
S
S
Bauer
M
M
Ryan
A M
AM
Sordat
B
B
Gibbs
V C
VC
Aguet
M
M
D000818:Animals; D002469:Cell Separation; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology; D005434:Flow Cytometry; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D053710:Interleukin-10 Receptor beta Subunit; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D011487:Protein Conformation; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D053701:Receptors, Interleukin-10; D013163:Splenomegaly / Q000276:immunology; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology; D014162:Transfection
C081846:IL10RB protein, human; D016898:Interferon-alpha; D053710:Interleukin-10 Receptor beta Subunit; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D007371:Interferon-gamma